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Evaluation of comfort using olopatadine hydrochloride 0.1% ophthalmic solution in the treatment of allergic conjunctivitis in contact lens wearers compared to placebo using the conjunctival allergen-challenge model.

PURPOSE: Olopatadine hydrochloride 0.1% ophthalmic solution is a topical antiallergy agent indicated for treatment of the signs and symptoms of allergic conjunctivitis. The purpose of this study was to evaluate the comfort of olopatadine used for contact lens wearers in the conjunctival allergen-challenge (CAC) model. METHODS: This was a single-center, randomized, double-masked, parallel-controlled CAC study. Contact lens-wearing subjects with a history of allergic conjunctivitis were randomized to receive olopatadine or placebo bilaterally. Fifteen minutes after study medication instillation, subjects inserted contact lenses. Allergen challenge was performed 10 minutes after contact lens insertion. Subjective evaluations of ocular comfort were obtained immediately and every minute after CAC, up to and including 10 minutes. Thereafter, comfort evaluations were made every 5 minutes up to and including 60 minutes. Subjects evaluated itching at 3, 7, and 10 minutes and redness was graded at 5, 10, and 20 minutes. All evaluations were graded on standardized scales. Subjects were given diaries in which to rate comfort at 2, 4, 6, 9, 12, and 13 hours and the time of contact lens removal. RESULTS: At post-study medication instillation, post-lens insertion, and at time points from 1 to 10 minutes post-allergen challenge, ocular comfort evaluations were statistically superior in subjects receiving olopatadine as compared with those receiving placebo (P < 0.05). The difference in time until contact lens removal was clinically significant, with subjects who were treated with olopatadine wearing lenses for an average of 2.1 hours longer than placebo group. CONCLUSIONS: As evidenced by significantly greater comfort and longer duration of lens wear, olopatadine provides superior comfort to contact lens wearers suffering from the signs and symptoms of seasonal allergic conjunctivitis, as induced by the CAC model.

Adult↗

Immunosuppressive effect of cholera toxin B on allergic conjunctivitis model in guinea pig.

PURPOSE: To investigate the new method of immunotherapy using cholera toxin B (CTB) in experimental allergic conjunctivitis. METHODS: We used 21 white Hartley guinea pigs. The animals were sensitized by intraperitoneal injection of ovalbumin (100 microg/mL) and albumin hydroxide (5 mg/mL) repeated after an interval of 2 weeks. One week after the second injection, conjunctivitis was induced by topical instillation of ovalbumin (5 mg/mL). The animals were divided into two groups, CTB group and control group. The CTB group underwent pretreatment of topical instillation of CTB (4 microg/30 mL) and ovalbumin (10 microg/30 mL), three times a day for 3 days, 1 week before the intraperitoneal injection. The control group did not undergo the pretreatment. Clinical examination was performed at 0.5, 6, and 24 hours after the development of conjunctivitis. Histological examination was performed at 6 and 24 hours. RESULTS: Both groups developed palpebral and bulbar edema with hyperemia 30 minutes after instillation of ovalbumin. The allergic reaction score was significantly less in the CTB group than in the control group (Mann-Whitney U-test: P <.01). The clinical reactions subsided after 6 hours. The CTB group showed less eosinophilic infiltration in the conjunctiva and the limbus, particularly in the conjunctival epithelium, than the control group at 6 and 24 hours. CONCLUSION: Pretreatment with topical CTB and antigen suppresses clinical and histological findings in experimentally induced allergic conjunctivitis.

Animals↗

Comparison of topical 0.05% levocabastine and 0.1% lodoxamide in patients with allergic conjunctivitis. Study Group.

PURPOSE: The aim of the study was to assess the efficacy and safety of 0.05% levocabastine eyedrops (H1 receptor blocker given BID + vehicle BID) compared with 0.1% lodoxamide ophthalmic solution (mast-cell stabilizer instilled QID) in reducing ocular signs and symptoms of allergic conjunctivitis. METHODS: A randomized, double-masked, parallel-group study was conducted in seven centres in France, in which 93 patients suffering from seasonal or perennial allergic conjunctivitis were randomly allocated to either 0.05% levocabastine (n = 47) or 0.1% lodoxamide (n = 46) in both eyes for a 14-day period. Efficacy was evaluated by subjective (prickling, burning, photophobia, itching) and objective (redness, chemosis, eyelid edema, tearing) sign scores at visits on days 7 and 14, and from data noted daily by the patient in a self-evaluation form. Safety was assessed as tolerance upon instillation and adverse event reports. RESULTS: The ocular allergy symptom and sign scores were comparable in the two treatment groups at baseline. With time, statistically and clinically significant reductions (p < 0.001) from baseline were observed for the subjective and objective scores, with no difference between the treatment groups. After the first instillation, signs were alleviated more rapidly in levocabastine-treated patients than in the lodoxamide group (p < 0.001). Overall assessments by the patient and investigator were similar in both groups. No serious adverse events were reported. CONCLUSIONS: Levocabastine ophthalmic suspension 0.05% (BID) appears to be as effective and safe as lodoxamide 0.1% (QID) in the management of allergic conjunctivitis.

Adolescent↗

High frequency of allergic conjunctivitis in myasthenia gravis without thymoma.

OBJECTIVES: To investigate the frequency of allergic disorders in myasthenia gravis (MG) patients and characterize the features of MG associated with allergic disorders. METHODS: Frequencies of past and present common allergic disorders in 160 MG patients who visited the Department of Neurology, Kyushu University Hospital from April 2000 to July 2003 and in 81 neurological normal controls were studied. RESULTS: Among various allergic disorders, the frequency of allergic conjunctivitis (AC) was significantly higher in MG patients (39/160, 24.4%, p(corr)=0.0112), especially with MG without thymoma (36/123, 29.3%, p(corr)=0.0016), in comparison to the controls (6/81, 7.4%). MG patients with AC showed a significantly higher rate of seronegative MG (43.6% vs. 17.4%, p=0.008) and a higher tendency of ocular MG (43.6% vs. 28.1%, p=0.071). Moreover, MG with AC had significantly lower anti-acetylcholine receptor antibody titers (median 6.8 nmol/l vs. median 23.6 nmol/l, p=0.0359) as well as a lower rate of coexisting thymoma (7.7% vs. 17.4%, p=0.016). The incidence of myasthenic crisis was also lower in MG with AC than without AC, yet the difference was not significant (7.7% vs. 15.7%). CONCLUSION: There was a significant association of AC with MG especially for ocular or seronegative MG in cases without thymoma.

Adult↗

Participation of chemical mediators in the development of experimental allergic conjunctivitis in rats.

In the present study, we investigated the participation of chemical mediators in the development of experimental allergic conjunctivitis in rats. Cetirizine (a histamine H1 receptor antagonist), ramatroban (a thromboxane A2 (TXA2) receptor antagonist) and zafirlukast (a cysteinyl leukotrienes (cys-LTs) receptor antagonist) were orally administered from day 14 to day 42 during repeated topical antigen challenge. An increase in reactivity to antigen- and histamine-induced eye scratching behavior was observed by topical sensitization in sensitized rats. Although increased reactivity to antigen was not influenced by cetirizine, ramatoroban and zafirlukast, increased reactivity to histamine was significantly inhibited by ramatroban. The development of conjunctival edema was also observed for topical sensitization. Cetirizine caused no inhibition of the development of conjunctival edema, but ramatroban and zafirlukast inhibited the development of conjunctival edema. In addition, the number of eosinophils in the conjunctiva was increased by topical sensitization. Cetirizine had no significant effect on the increase in the number of eosinophils. However, ramatroban and zafirlukast were effective in inhibiting an increase in the number of eosinophils induced by topical sensitization. These results indicate that TXA2 is involved in increased histamine reactivity, and TXA2 and cys-LTs are associated with not only the conjunctival edema but also eosinophil infiltration during the development of experimental allergic conjunctivitis in rats.

Administration, Oral↗

Lodoxamide versus spaglumic acid: a comparative double-blind trial on patients suffering from seasonal allergic conjunctivitis induced by Parietaria pollen.

In order to evaluate the efficacy and tolerability of lodoxamide in the treatment of allergic conjunctivitis, the authors conducted a double-blind trial with intrapatient comparison on 32 patients, using lodoxamide versus spaglumic acid in the course of two conjunctival provocation tests performed with specific allergens. The patients received one drop of lodoxamide in one eye and one drop of spaglumic acid in the other; 15 minutes later, 25 microliters of allergen extract at a pre-established concentration was instilled. After 10 minutes, the signs and symptoms of the allergic response were evaluated and recorded. Six hours later, the instillation of the allergen extract in both eyes was repeated following the same procedure, to establish the duration of the effect of the two drugs. The results, obtained by evaluating the main clinical signs and symptoms (itching, lacrimation, hyperaemia, palpebral oedema and chemosis), demonstrate with statistically significant differences that lodoxamide inhibits the conjunctival response to exposure to the allergen with greater efficacy than spaglumic acid, and for a longer duration. The two drugs provided similar and satisfactory tolerability. In view of these results, lodoxamide can definitely be considered and effective drug in the treatment of allergic conjunctivitis.

Adult↗

Allergic conjunctivitis as a risk factor for laser in situ keratomileusis.

PURPOSE: To analyze the effect of allergic conjunctivitis (AC) on the outcome of laser in situ keratomileusis (LASIK) in myopic eyes. SETTING: Minamiaoyama Eye Clinic, Tokyo, Japan. METHODS: Patients who had LASIK were divided into 2 groups: those with AC (84 eyes of 49 patients; the allergic group) and those without AC (140 eyes of 77 patients; the nonallergic group). Allergic conjunctivitis was diagnosed clinically by symptoms of eye itching and clinical findings such as papillary proliferation on the tarsal conjunctiva. Preoperative and postoperative uncorrected visual acuity (UCVA) and refraction and intraoperative and postoperative complications were compared. RESULTS: There were no significant differences in UCVA and refraction between the 2 groups. No complications were observed in the allergic group. Intraoperative conjunctival chemosis (3 eyes of 2 patients) and a postoperative epithelial defect that resulted in epithelial ingrowth (1 eye) were observed in the nonallergic group. CONCLUSION: The findings suggest that AC is not a risk factor for LASIK.

Adult↗

Topical sodium cromoglycate (Opticrom) relieves ongoing symptoms of allergic conjunctivitis within 2 minutes.

Twelve patients with seasonal allergic conjunctivitis caused by either birch or timothy grass pollen were challenged out of season in both eyes, with the relevant allergen. Itching, redness, swelling, and tearing were assessed on a 0-3 scale. When a positive reaction, i.e., at least 4 points, had occurred in both eyes, one drop of 2% sodium cromoglycate was administered to one eye and one drop of placebo to the other eye in each patient, in a double-blind, randomized fashion. Symptoms were then assessed after 2, 10, 30, and 60 min. Sodium cromoglycate was statistically better than placebo in reducing the symptoms at 2, 10, and 30 min after the treatment had been administered, showing that topical application of 2% sodium cromoglycate can quickly relieve ongoing symptoms of allergic inflammation in the eye.

Administration, Topical↗

[Induction of oral tolerance to experimental allergic conjunctivitis in rats].

Immunological tolerance can be induced by the oral administration of antigen. We induced oral tolerance rats to experimental allergic conjunctivitis by ovalbumin and investigated the suppression of inflammation. In groups which had started eating antigen both before and after the immunization, the serum anti-ovalbumin IgE level measured by passive cutaneous anaphylaxis reaction was significantly lower than in a group that had not been fed antigen. The intensity of experimental allergic conjunctivitis in the group which had started eating antigen before immunization, was significantly suppressed in regard to the leakage of Evans Blue from conjunctival vessels 30 minutes after the challenge and the neutrophil infiltration 6 hours after. The dye leakage of the group which had started feeding after immunization was also significantly suppressed. There was a positive correlation between the serum IgE level and the leakage of Evans Blue (r = 0.90, p < 0.001). These results suggest that the suppression of antigen-specific IgE antibody production caused by oral tolerance affected the decrease of local inflammation on the conjunctiva.

Administration, Oral↗

[Nedocromil sodium as a topical treatment of allergic conjunctivitis due to grasses].

Thirty-two patients (20 males and 12 females, mean age 31 ys) with seasonal allergic conjunctivitis to grass pollen, were selected for this study. Nedocromil sodium 2% ophthalmic solution was given at the dosage of 1 drop four times a day for four weeks during the month of June. On a daily diary card each patient had to report the severity of the symptoms: itchy eyes, lacrimation, red eyes and photophobia, following an arbitrary score from 0 to 3 (0 = no symptom, 1 = mild, 2 = medium, 3 = severe). After four weeks of treatment we observed a statistically significant improvement of the symptoms considered. Patients did not take other medications and did not report any side effects. Nedocromil sodium is therefore a valid alternative in the treatment of allergic conjunctivitis to grass pollen.

Administration, Topical↗

[Evaluation of astemizole in allergic conjunctivitis].

A 4 week open study was carried out to evaluate the efficacy and safety of astemizole in the treatment of allergic conjunctivitis 31 patients were included in the study. Global efficacy, with 10 mg astemizole OD, was rated good or excellent in 100% of treated patients. A marked improvement of the main symptoms was noted at day 15. No side effects whether of the anticholinergic type or of the drowsiness type, were observed during the whole study. Astemizole appears to be a particularly interesting symptomatic treatment of allergic conjunctivitis.

Adult↗

A randomized, double-masked, placebo-controlled parallel study of 0.2% loteprednol etabonate in patients with seasonal allergic conjunctivitis.

BACKGROUND: Loteprednol etabonate is a site-active corticosteroid with efficacy and safety in treating ocular inflammation at the 0.5% concentration. Evidence from dose-response studies suggested that the 0.2% concentration might be effective in treating ocular allergy. OBJECTIVES: The objective of this study was to evaluate the effects of 0.2% loteprednol etabonate in reducing the signs and symptoms of seasonal allergic conjunctivitis. METHODS: This was a randomized, double-masked, placebo-controlled, parallel-group multicenter study. Patients with signs and symptoms of environmental seasonal allergic conjunctivitis received either loteprednol etabonate or placebo bilaterally four times daily for 42 days. RESULTS: Enrolled were 133 patients (66 receiving loteprednol etahonate; 67 receiving placebo). A reduction in severity was seen in both loteprednol etabonate and placebo groups for bulbar conjunctival injection (1.3 vs 0.9 units on a 0 to 3 scale) and itching (3.5 vs 3.1 units on a 0 to 4 scale) over the first 2 weeks. The treatment effect was -0.5 and -0.6 units in favor of loteprednol etabonate (P < .001). Resolution (the proportion of patients with the sign or symptom no longer present) at visit 4 (day 14) strongly favored loteprednol etabonate-treated patients over placebo-treated patients (31% and 9%, and 54% and 38%, for injection and itching, respectively). Both treatments were well tolerated. No patients in either treatment group (0 for loteprednol etabonate and 0 for vehicle) had an elevation of intraocular pressure of 10 mm Hg or greater during the 6 weeks of treatment. CONCLUSIONS: Loteprenol etabonate (0.2%) was more effective than placebo in the treatment of seasonal allergic conjunctivitis. Loteprednol etabonate (0.2%) had a safety profile comparable to placebo during this 6-week trial.

Adult↗

A chronic model for evaluating the itching associated with allergic conjunctivitis in rats.

The present study was performed to develop a new model for evaluating itching associated with allergic conjunctivitis in rats. Repeated topical application of antigen caused an increase in eye scratching behavior in sensitized animals, and a significant difference was observed from days 21 to 42. Almost the same findings were observed in allergic symptoms, hyperemia and edema. Instillation of histamine also resulted in an increase in eye scratching behavior. The sensitivity to histamine in eye scratching behavior was increased by topical antigen application for 42 days after sensitization. In addition, the number of conjunctival eosinophils was significantly increased by repeated topical antigen application from days 21 to 42 in sensitized rats. Some anti-allergic drugs such as olopatadine (H1 antagonist), cetiridine (H1 antagonist) and ramatroban (thromboxane A2 (TXA2) antagonist) caused an inhibition of eye scratching behavior induced by topical sensitization in a dose-related manner. However, zafirlukast (cys-LT antagonist) caused no significant inhibition even at a dose of 30 mg/kg. The findings in present model of itching in allergic conjunctivitis were mainly through histamine H1-activity, and thromboxane A2 receptors were also involved in the response.

Animals↗

A double-masked comparison of ocular decongestants as therapy for allergic conjunctivitis.

A prospective, randomized, double-masked study of three commercially available ocular decongestant products was conducted to compare their relative efficacies in the treatment of allergic conjunctivitis. All three products contained a vasoconstrictor (naphazoline hydrochloride) and an antihistamine (antazoline phosphate or pheniramine maleate) in varying concentrations. Eighty-nine (89) patients presenting the ocular signs and symptoms of allergic conjunctivitis were enrolled and randomly distributed among the three treatment groups. Patients were evaluated for three ocular signs (lid swelling, bulbar conjunctival inflammation and palpebral conjunctival inflammation) and three ocular symptoms (itching, tearing and discomfort). An overall follow-up impression of treatment results was also recorded. The treatment period lasted one week. The three preparations were found to vary greatly in patient comfort and acceptability but were not different in their ability to ameliorate the itching, tearing, redness, edema and discomfort when dosed topically for the relief of allergic conjunctivitis.

Antazoline↗

A comparative trial of the safety and efficacy of 0.1 percent pemirolast potassium ophthalmic solution dosed twice or four times a day in patients with seasonal allergic conjunctivitis.

PURPOSE: To compare efficacy and safety between twice-daily and four-times-daily regimens of pemirolast 0.1% in allergic conjunctivitis patients. METHODS: This investigator-masked trial recruited 169 patients, with a positive skin prick test, +2 itching and hyperemia. Patients were randomized to two times daily (t.i.d.) or four times daily (q.i.d.) treatment during allergy season. Evaluation was at 0, 2 and 4 weeks, with itching and hyperemia at week 4 as the primary endpoints. Analysis used last observation carried forward (LOCF) and analysis of variance (ANOVA) for efficacy, factoring treatment and center variations. The basis of the statistical evaluation was to confirm parity between two treatments, via noninferiority hypothesis testing. A 95% confidence interval (CI) with an upper limit of < or = 0.5 was set to assess non-inferiority or to conclude if schedules were statistically similar. RESULTS: B.i.d. and q.i.d. baselines were similar, respectively, for itching (2.6 and 2.8) and hyperemia (2.3 and 2.2). Week 4 itching was statistically non-inferior between treatments (1 b.i.d. versus 0.8 q.i.d.), with a mean treatment difference of 0.17 (-0.13, 0.47, Delta < or = 0.5). Week 4 hyperemia was comparable (1.2 for b.i.d. versus 1.0 for q.i.d). Week 2 scores and mean change from baseline (weeks 2 and 4), patient diary data, and investigator assessments were comparable. Both regimens were well tolerated with no differences in adverse events were observed. CONCLUSIONS: B.i.d. dosing was statistically non-inferior to q.i.d. dosing with respect to itching and hyperemia. Both regimens were similarly well tolerated in allergic conjunctivitis patients.

Adolescent↗

Effects of ketotifen 0.025% and lodoxamide 0.1% on eosinophil infiltration into the guinea pig conjunctiva in a model of allergic conjunctivitis.

The effects of ketotifen and lodoxamide on eosinophil infiltration were assessed in a guinea pig model of allergic conjunctivitis. The two active treatments were coded in this masked study in which 30 male guinea pigs, sensitized to chicken egg albumin (ovalbumin), were randomly assigned to one of three groups: Group 1, instillation of 0.9% NaCl into the conjunctival sac of both eyes; Group 2, instillation of 0.025% ketotifen into the left eye and 0.9% NaCl into the right eye; Group 3, instillation of 0.1% lodoxamide into the left eye and 0.9% NaCl into the right eye. Ovalbumin was administered topically to each eye, except in Group 1 where it was only applied to the left eye. (111)In-oxine labeled eosinophils were injected into the jugular vein of each guinea pig; the animals were sacrificed 17 hours after ovalbumin had been applied. The level of radioactivity in the ketotifen- and lodoxamide-treated eyes was approximately 60% of that in the saline-treated eyes. Moreover, the mean level of radioactivity in the ketotifen- and lodoxamide-treated eyes was comparable with the mean level of radioactivity in the saline-treated eye of Group 1, which had not been exposed to allergen. These results indicate that the therapeutic effects of ketotifen and lodoxamide in allergic conjunctivitis may be partly mediated by an inhibitory effect on eosinophils.

Administration, Topical↗

Allergic conjunctivitis.

The purpose of this research is to study the clinical features and risk factors of various types of allergic conjunctivitis. Four hundred and forty-five patients with a history of itching, foreign body sensation, lacrimation and red eyes were examined, and a skin test was performed and assessed to grade the severity. The mean age of the subjects was 24.5 +/- 16.3 years with female preponderance, except for vernal keratoconjunctivitis. The majority of the patients had perennial allergic conjunctivitis. Ninety-five percent of the patients had associated allergic diseases, especially allergic rhinitis. Sixty-six percent of the patients had a family history of atopy. Most patients had symptoms at night. Symptoms persisted throughout the year and were generally triggered by exposure to house dust. The allergy skin tests to common aero-allergens were positive in 95% of patients tested. Common allergens causing sensitization were house-dust mites, house dust, cockroaches, and grass pollen. Environmental control and avoidance of these allergens should be stressed in the management of these conditions.

Adolescent↗

A multicenter comparison of the ocular efficacy and safety of diclofenac 0.1% solution with that of ketorolac 0.5% solution in patients with acute seasonal allergic conjunctivitis.

Only one of several available ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) is currently FDA approved for use in acute seasonal allergic conjunctivitis (SAC). Sixty patients with SAC and moderate itching and bulbar conjunctival injection were enrolled in a multicenter, randomized, double-masked, parallel-group trial comparing diclofenac sodium (DS) with ketorolac tromethamine (KT). Patients instilled 1 drop four times daily while awake for 14 days. Ocular signs and symptoms were evaluated at one and two weeks. The primary efficacy variables were itching and bulbar conjunctival injection. For both treatments, the ocular allergy sign and symptom scores were comparable at baseline. Both treatments evaluated in this study were well tolerated. Significant clinical and statistical reductions from baseline were observed in the primary efficacy variables. Treatment group differences were observed for the pain/soreness score with an advantage observed for the DS group at 30 minutes and at day 7. Our conclusion is that diclofenac sodium and ketorolac tromethamine acted similarly to reduce the ocular signs and symptoms associated with acute seasonal allergic conjunctivitis. There was a statistically significant advantage for the DS group to be free of symptoms at the day 7 visit as compared to the KT group (20.7% vs. 3.2%).

Acute Disease↗